The long term objective goal of this proposal is to gain insight into mechanisms of innate and adaptive immunity to microbes in skin. In inflammatory acne, Propionibacterium acnes plays a key role in eliciting host inflammatory response that is thought to be important for the pathogenesis of the disease. Recent data indicate that P. acnes activates the innate immune system, macrophages and polymorphonuclear leukocytes (PMNs) via Toll like receptor 2 (TLR2) to release proinflammatory cytokines. In addition, preliminary results suggest that granulysin, a product of adaptive immune T cell response is able to kill P. acnes directly. They propose experiments to investigate the role of TLRs and granulysin in pathogenesis of acne. They hypothesize that TLRs induce antimicrobial activity of PMNs, important cellular component of innate immunity. Furthermore, they hypothesize that adaptive immune system plays a role in controlling P. acnes growth by releasing granulysin. Better understanding of the innate and adaptive immune mechanisms against P. acnes could provide insight into host defense mechanisms in skin and suggest development of novel avenues of immunologic intervention in acne.